探討缺乏二十二碳六烯酸對雄性大鼠由壓力誘發糖皮質類固醇分泌之影響

Abstract

本論文主要探討飲食中缺乏n-3多元不飽和脂肪酸對大鼠腦區二十二碳六烯酸含量及經由壓力誘發之神經內分泌路徑─下視丘-腦下垂體-腎上腺路徑反應的影響。 利用Sprague-Dawley雄性大鼠，在離乳之後給予n-3多元不飽和脂肪酸缺乏或正常的飼料7週。觀察其腦區二十二碳六烯酸含量的變化，並以行為實驗檢驗兩組大鼠在焦慮及憂鬱相關行為的表現。透過給予大鼠束縛壓力1小時後，檢測其下視丘-腦下垂體-腎上腺路徑的反應。大鼠於犧牲後分析各腦區DHA含量、血清中糖皮質類固醇的含量、糖皮質類固醇受體蛋白及brain-derived neurotrophic factor (BDNF)蛋白在海馬及下視丘的表現。實驗結果發現在離乳後攝取缺乏n-3多元不飽和脂肪酸飼料的大鼠，不論在海馬、下視丘、前額葉皮質、杏仁核、腦幹及肝臟，二十二碳六烯酸的含量均較正常組顯著地降低。然而在焦慮或憂鬱相關行為的檢測上兩組並無差異。在給予束縛壓力後，血中糖皮質類固醇的濃度在攝取n-3多元不飽和脂肪酸缺乏飼料的組別明顯較高。但在海馬及下視丘的糖皮質類固醇受體蛋白表現量並無差異，而BDNF蛋白於海馬的表現量在壓力後，缺乏n-3多元不飽和脂肪酸的組別會較正常組別下降。綜合以上，本論文主要發現雄性大鼠離乳後，攝取缺乏n-3多元不飽和脂肪酸飼料7周會造成各腦區二十二碳六烯酸含量顯著下降，及增加由壓力誘發的糖皮質固醇分泌。

Most previous studies have focused on rat docosahexaenoic acid (22:6n-3, DHA) deficiency created during brain development via maternal n-3 fatty acid-deficient diet from pregnancy and lactation on adult anxiety and depression behaviors. It has been suggested the anxiety and depression is associated with hypothalamic-pituitary-adrenal axis (HPA axis) responses. The aim of this study was to evaluate whether brain DHA deficiency during post-weaning period would enhance restrain-induced HPA axis responses and anxiety or depression-like behavior in adult male rats. After weaning at postnatal day 21, male rats fed an n-3 fatty acid-deficient or an n-3 fatty acid-adequate diet till sacrificed at postnatal day 70. The DHA levels were significant decreased in hypothalamus and hippocampus and other brain regions in rats fed with n-3 fatty acid-deficient diet compared to the rats fed with n-3 fatty acid-adequate diet during post-weaning period for 7 weeks. The anxiety-like behavior in the elevated plus-maze test and depressive-like behavior in the forced swim test were no difference between groups. The restraint-induced rectal temperature was increased during the restraint, but no difference between groups. The serum corticosterone was significant increased right after restraint in rats fed an n-3 fatty acid-deficient diet. The GR expression in hippocampus and hypothalamus were no difference between groups. The BDNF was significant decreased in hippocampus after restraint in rats fed n-3 fatty acid-deficient diet compared to the rats fed n-3 fatty acid-adequate diet. This study suggest that brain DHA level can be decreased in male rats fed n-3 fatty acid-deficient diet during post-weaning period, and the decreased brain DHA is associated with higher stress-induced serum corticosterone levels.